ISPAD 2022 Sick Day Management Guidelines

Machine Translated by Google
ISPAD CLINICAL PRACTICE CONSENSUS GUIDELINES 2022
ISPAD Clinical Practice Consensus Guidelines 2022: Sick day management in children
and adolescents with diabetes
Helen Phelana ,Jamie

Ragnar Woodj , Sabine E. Hoferc , Steven Jamesd, Alanna Landrye , Warren Leef ,
R. Hanasb
, Ethel Codnerh
at John Hunter Children's Hospital, Newcastle, New South Wales, Australia

b
Department of Pediatrics, NU Hospital Group, Uddevalla Hospital, Uddevalla, and Sahlgren ska
Academy, Institute of Clinical Sciences, University of Gothenburg
vs
Department of Pediatrics, Medical University of Innsbruck, Austria

d
University of the Sunshine Coast, Petrie, Queensland, Australia
e
Department of Paediatrics, Oak Valley Health, Markham, Ontario, Canada
f
Dr Warren Lee's Paediatrics, Growth & Diabetes Centre, and KK Hospital, Singapore j
University Hospitals Rainbow Babies and Children's Hospital, Case Western Reserve University,
Cleveland, Ohio, United States
h
Institute of Maternal and Child Research (IDIMI), School of Medicine, University of Chile,
Santiago, Chile
Corresponding author:
Ethel Codner, MD, Institute of Maternal and Child Research (IDIMI), School of Medicine, University of
Chile. Santa Rosa 1234, Postal Code: 8360160, Santiago, Chile. Email: ecod ner@med.uchile.cl.
Phone: 562-29770855. Fax: 562-24248240.
Running title: Sick Day Management in Diabetes
Key Words: Type 1 diabetes, Pediatrics, Sick day management, Ketones, and DKA
Word count: 6649

Figures: 3
Boards: 2
References: 75
1
1. WHAT'S NEW IN SICK DAY MANAGEMENT?
2. EXECUTIVE SUMMARY AND RECOMMENDATIONS
3. THE EFFECT OF ILLNESS ON DIABETES
4. SICK DAY DIABETES MANAGEMENT PRINCIPLE
5. PREPARATION FOR SICK DAYS
6. DIABETES MANAGEMENT FOR MILD ILLNESS AND KETOSIS
PREVENTION
7. SICK-DAY MANAGEMENT WHEN VOMITING AND/OR GASTROINTESTI
NAL TRACT INFECTION
1. WHAT'S NEW IN SICK DAY MANAGEMENT?
• This new version of the sick-day guidelines gives a greater emphasis on how to manage
diabetes for prevention of ketones and management with new technologies.
• Emerging infections such as COVID 19, and even vaccinations for COVID 19, can
precipitate persist increases in insulin requirements for days or weeks.
• Anticipatory guidance to deal with conditions of predictable patterns of increased in
sulin requirements, such as chronic conditions requiring steroid therapy or hyperglyce
mia associated with menstrual period, will reduce anxiety and unnecessary morbidity.
• Use of electronic data sharing platforms will help families and health care teams assist
with sick day management.
• Closed-loop technologies, combining both pumps and sensors, and their interactive
regulation by artificial intelligence systems (hybrid closed loop systems, automated in
sulin delivery or AID), may be helpful to keep the glucose levels in target during sick
2
days; particularly those systems that incorporate customizable glucose targets and
user-initiated modes to reduce or intensify insulin delivery in special situations.
2. EXECUTIVE SUMMARY AND RECOMMENDATIONS
2.1. Sick day preparation
People with diabetes, their families and/or caregivers
• must receive education and be given access to guidelines preparing them for managing
diabetes during illness. This education should be delivered at diagnosis, at follow-up at
at least annually, and opportunistically [C].
• should be taught to proactively adjust diabetes therapy to prevent uncontrolled or symp
tomatic hyperglycemia, dehydration, hyperglycemic ketosis, ketoacidosis, hypo
normoglycemic ketosis and/or severe hypoglycemia [E].
2.2. Management for ketosis prevention
• Never completely stop insulin! Replace insulin pen cartridge and needle, or pump car
bridge, line and catheter to ensure adequate insulin delivery [B].
• Monitor glucose and ketone levels at least 1-2 hourly.[E]
• Monitoring blood ketones is preferred over urine ketones, and the use during illness can
reduce emergency room visits and hospitalizations [B].
• Aim for a glucose levels between 3.9-10 mmol/l (70-180 mg/dl) and blood ketones
below 0.6 mmol/l [E].
• Adjust the insulin dose in response to glucose and blood ketone levels [E].
• Insulin doses may need to be increased considerably during illness in children who are
in the partial remission or 'honeymoon' phase, when doses are relatively low [E].
• Maintain hydration and seek urgent medical advice if the child is unable to drink
3
o Oral fluids containing carbohydrate should be consumed if the glucose level
is below 14 mmol/l (250 mg/dl); carbohydrate-free fluids should be given
when glucose is above 14 mmol/l (250 mg/dl).
o Consider timely initiation of intravenous fluids if the child is unable to drink
[E].
• Minor illnesses managed effectively at home will reduce the impact and costs on health
services and the family [E].
• However caregivers must be supported to seek medical review and treatment if [E for
all below]:
o the child's condition deteriorates
o the underlying condition is unclear
o fever persists
oh caregiver understanding/language problems make it difficult to com
communicate with the family
o the family does not have the resources to manage the illness at home
oh there are co-morbid conditions (eg Down Syndrome, disordered eating
behaviors, mental illness, epilepsy, inflammatory bowel disease, ma
laria, parasitic infections, etc.)
o the child is very young (less than 5 years old)
o parents are unable to keep glucose level above 3.9 mmol/l (70 mg/dL)
2.3. Management when vomiting and/or gastrointestinal illness present
• Consider nausea and/or vomiting as a sign of insulin deficiency until proven otherwise
[E].
4
• Hypoglycemia with hyperketonemia, which may occur in the setting of gastrointestinal
nal llness or starvation, requires administration of insulin along with carbohydrate
intake [E].
• Gastrointestinal illnesses, especially gastrointestinal viruses, are the most frequent
cause of hypoglycemia during sick-days and may require decreasing insulin doses. [
• Seek URGENT specialist medical review in an emergency setting if [E for all below]:
o weight loss continues, suggesting worsening dehydration and potential cir
compromised culatory
o vomiting persists beyond two hours (particularly in young children)
o unable to keep glucose level > 3.9mmol/mol (70mg/dl)
o if hypoglycemia cannot be corrected, refer for intravenous fluids with dex
trose along with continued monitoring.
2.4. Management where ketosis suspected or confirmed
• Give small amounts of liquids containing water and electrolytes every 5-10 minutes,
carbohydrate-containing drink if glucose level is below 14 mmol/l (250 mg/dl). Aim
for 4-6mls/kg/hour.
• Give frequent additional doses of ultrarapid, rapid-acting or short-acting insulin to treat
ketosis and prevent progression to ketoacidosis and hospital admission.
• Seek URGENT specialist medical review in an emergency setting if [E for all below]:
o glucose level continues to rise despite extra insulin doses
o fruity breath odor (acetone) detected or worsens
o blood ketones remain elevated (>1.5 mmol/L) or urine ketones remain large
despite extra insulin and hydration
o the child or adolescent is becoming exhausted, confused, hyperventilating
(kussmaul breathing), or has severe abdominal pain
5
o there is a change in neurologic status, mental confusion, loss of consciousness,
seizures, or progression of confusion to avoid potential for cerebral edema
and/or cerebral injury; treatment of cerebral edema and cerebral injury is a med
ical emergency requiring immediate assistance with advanced medical facilities
to prevent morbidity and mortality
• Transport should be facilitated as soon as possible according to local circumstances.
• The diabetes team should contact local medical personnel, to ensure systems in place
for initial glucose and electrolyte monitoring along with intravenous fluids and insulin
for emergency.
2.5. Specific advice regarding sick day management where diabetes technology (insulin
pump, hybrid closed loop systems, glucose sensors) is used
• Continuous glucose monitoring (CGM) devices or intermittently scanned glucose mon
itoring devices (isCGM), can preferably be used to supplement blood glucose monitor
ing if available [E].
• The use of insulin pumps, including both closed loop and hybrid models, can be con
continued in hospital when health care teams are familiar with the technology, there is
access to adequate insulin pump supplies, and/or the person and/or their caregiver can
continue to safely operate the pump.
• In the presence of high glucose level and vomiting and or ketonaemia, closed loop
should be stopped and sick day management should run in open loop or manual mode
following regular sick day rules.
3. THE EFFECT OF ILLNESS ON DIABETES
Children and youth who have optimal diabetes management should not experience more illness
or infections than peers without diabetes. However, even routine childhood illnesses
6
complicate diabetes management and increase the risk for diabetic ketoacidosis (DKA) or hy
polyglycemia (with gastroenteritis). While there are very few studies about intercurrent illness
in type 1 diabetes (T1D), one study involving adults with T1D reported a higher risk of urinary
tract, bacterial skin, or mucous-membrane infections, although upper respiratory-tract infec
tions were no more frequent in adults with type 1 diabetes than in controls. 1 There is some
evidence of impaired leukocyte function with impaired metabolic control, and children with
sub-optimal diabetes management may have altered immune function, increasing susceptibility
2
to and delayed recovery from infection. One pediatric study found low IgG concentrations
and reduction in complement protein 4, variant B (C4B) levels related to impaired metabolic
3 controls.
Most illnesses, particularly where there is fever, raise blood glucose levels due to higher levels
of circulating stress hormones which promote glycogenolysis, gluconeogenesis, and insulin
resistance. 4
Illness often increases ketone body production due to inadequate insulin levels
and the counter-regulatory hormone response. In contrast, illness associated with vomiting and
diarrhea (eg viral gastroenteritis) may lower glucose levels with the increased possibility of
hypoglycemia rather than hyperglycemia. Decreased food intake, poor gastric absorption, de
layed gastric emptying, and/or overt diarrhea with more rapid transit time during gastroenteritis
may contribute to hypoglycemia risk. Insulin requirements may increase during the incubation
period of an infection for a few days before the onset of symptoms. Also, the increased
need for insulin may persist for a few days after symptoms have passed. However, insulin
needs are highly variable from one person to another and from one illness to the next. During
a typical viral "epidemic," however, patterns may occur that facilitate making some generali
zations to help advise subsequent persons/families.
7
Emerging infections such as COVID 19, and even vaccinations for COVID 19, can precipitate
persistent increases in insulin requirements for days or weeks. Insulin doses of up to 2.2
units/kg/day may be required during peak inflammatory response to maintain normoglycemia,
but rapid reduction of doses may be needed on recovery. In the case of COVID 19, it may be
wise to ask families about respiratory symptoms in the setting of unexplained hyperglycemia
5-8
in a previously stable person with diabetes.
Some conditions are associated with insulin resistance: children with chronic conditions re
quiring steroid therapy will sometimes experience predictable patterns of increase insulin re
quirements. 9 Similarly, some women will routinely experience hyperglycemia around and dur
ing their menstrual periods. In one study, 67% of women experienced changes in blood glucose
10
levels or glycosuria premenstrually and 70% during the menstrual phase. An exposure to a
gluten containing meal in a person with celiac disease may precipitate a period of prolonged
hyperglycemia with or without abdominal pain and loose stools, and this possibility must be
considered with a history of similar recurring episodes. The hyperglycemia may last overnight
11-14
and require “sick day” doses of insulin.
4. SICK DAY DIABETES MANAGEMENT PRINCIPLES
4.1. Sick day guidelines should be taught soon after diagnosis and reviewed at least annually.
See below section '5. Preparation for sick days.'
4.2. Monitor glucose levels frequently.
Frequent glucose monitoring facilitates optimal management during illness (with adult super
vision, even in adolescents). Glucose should be monitored every 1-2 hours. Insulin adjustments
take place in direct relationship to the ongoing glucose and ketone monitoring results.
8
CGM use in children, adolescents and young adults has tremendously increased within the past
years in well-resourced countries 15. CGM technology has significantly improved to greater
accuracy and convenience and is more and more used without confirmatory blood glucose
monitoring. CGM devices are more effective in detecting trends towards hyper- and hypogly
16 17
cemia, , which appears very useful in sick day management, as the CGM device can signal
whether the glucose is continuing to rise, fall, or is remaining stable. However, one needs to
be aware of limitations and possible interference with drugs used in sick day management (eg
18 .
acetaminophen, ascorbic acid, salicylic acid) and the used CGM device In this case, blood
glucose measurements are still necessary, accompanied by ketone measurements in urine
and/or blood. In addition, hypoperfusion from dehydration can also decrease the accuracy of
the CGM. Parents and adolescents should maintain attention to glucose trends, ensuring the
diabetes care team has access to shared data where possible, and that parents are followers of
their child's/adolescent's glucose patterns if possible.
4.3. Monitor ketones, ideally by finger prick blood test
Ketones are produced by the liver from free fatty acids that are mobilized as an alternative
energy source when there is lack of glucose for intracellular metabolism, either from inade
quate intake or inability to utilize glucose in the setting of insulin deficiency. Starvation ke
tones are produced when the blood glucose is low. Ketones are also produced when insulin is
lacking to initiate the transport of glucose from the blood stream into the cell. Accu Ketones
mulate because of increased lipolysis and increased ketogenesis, due to low insulin levels and
elevated counter-regulatory hormone levels.
There are three ketones: acetoacetate, acetone, and beta-hydroxybutyrate. Urine ketone strips
measure acetoacetate (AcAc) and acetone (if the strip contains glycine), while laboratories and
blood ketone strips measure beta-hydroxybutyrate (BOHB), the predominant ketone in DKA.
9
Home measurement of blood BOHB concentrations in children and adolescents enables earlier
identification and treatment of ketosis compared to urine ketone testing, and decreases diabetic
19-21 Family
tes-related hospital visits (both emergency department visits and hospitalizations).
lies should be encouraged to have home blood ketone test strips. However, blood ketone strips
can be unaffordable for many households, may not be covered by insurance programs, or may
not be available. In these circumstances, urine ketone strips can be used for sick day manage
is lying. In countries where diabetes is uncommon, or a low priority, persons/families should be
encouraged to carry blood ketone strips with their meter or urine ketone strips to hospital if the
child needs admission, in case the hospital does not have the facilities for ketone testing.
• Adult studies have shown that the time delay after an insulin pump stop to diagnose
22 and that uri

ketosis is significantly longer for ketonuria than for plasma ketonaemia
nary ketone tests can remain positive more than 24-hours after resolution of ketoacido
located in the majority of persons. 23
• There can be a dissociation between urine ketone (AcAc) and blood BOHB concentra
tions such that urine ketone tests can still be negative or show only trace or small ketone
levels when blood BOHB is already high, indicating need for treatment. 19.24
• Following resolution of DKA, the dissociation between urine ketones and blood ke
tones continue as urine ketone levels remain elevated, and can lead to excess insulin
administration and risk for hypoglycemia if treatment is based on the urine ketone result
rather than the blood ketone result.
Urine ketone strips are inexpensive but may deteriorate within a month or so after opening the
bottle, so care may be needed to ensure a fresh bottle is available if the previous bottle had
been opened more than a month prior.
Blood BOHB monitoring can be especially useful in very young children, who cannot provide
urine on demand, or in others who find giving urine samples difficult. Continuous ketone
10
measurement that occurs alongside continuous glucose measurement is in research develop
ment, and not yet clinically available.
4.4. Monitor and maintain hydration with adequate salt and water balance.
Hyperglycemia, fever, excessive glycosuria, and ketonuria all contribute to increased fluid
losses. Prevention of dehydration should be a priority during sick days.
4.5. Do not stop insulin. Remind the family that T1D is a condition caused by lack of insulin,
not glucose excess. The insulin dose may need to be increased or decreased to maintain glucose
metabolism, but it should never be stopped. The most common mistake made by health care
teams and caregivers who are unfamiliar with diabetes, is to recommend the complete omission
of insulin because "the child is ill and not eating” or “the blood glucose is low” thus increasing
the risk of frank DKA. 4.24-26. Even in the fasting state, insulin is required for basal metabolic
needs, which may go up during an acute illness, when counter-regulatory stress hormones are
elevated.
4.6. Treat any underlying, precipitating illness.
The underlying illness should be treated as recommended for any child or adolescent without
diabetes (ie antibiotics for bacterial infections, etc.). Fever, malaise, and headache can be
treated with antipyretics or pain medications such as paracetamol (ie acetaminophen) or ibu
profen, unless there are allergies to these medications. Families can be advised to include ac
etaminophen suppositories with their sick day supplies for use when enteral intake may be
difficult, such as with gastroenteritis. Acetaminophen or acetaminophen-containing cold med
ications can cause interference in some CGM devices. 27.28 However, some newer generations
of CGM no longer experience acetaminophen interference. 18.29
5. PREPARATION FOR SICK DAYS (FIGURE 1)
5.1. sick day education
11
All families should receive education about sick day management and have access to guide
lines on sick day management. At diabetes diagnosis, families can be overwhelmed with new
information, and find it difficult to retain information about sick day management post diag
nosis. 30
For this reason the information at diagnosis should be simple, focusing on the im
portance of frequent monitoring and not stopping insulin during an illness, and contacting the
health care teams early for advice. As families become more competent with their diabetes
care, the sick day management education should be repeated at least annually. Intensive train
31
ing in sick-day rules have shown to decrease the incidence of DKA.
The health care team should tailor the education to suit the age of the child/adolescent and
32
development stage. For very young children, families should receive appropriate advice on
managing gastroenteritis and the need for early intervention and possible mini-dose glucagon
33
(TABLE 2). Older teens should receive sick day management education in a format that is
most readily available to them as they become more independent in their diabetes self-man
aging, although families should be advised to manage the diabetes tasks during illness re
gardless of age, as managing any intercurrent illness is challenging without support and guidance
ance.
5.2. Sick day supplies
Households should maintain supplies of glucose and ketone monitoring strips, insulin, and an
emergency glucagon kit/supply of nasal glucagon, and have a sick day management plan either
in electronic or paper format, with clear guidance on:
• glucose targets and insulin adjustments
• fluid/hydration requirements including what type of fluid to offer, how often fluid,
and food should be offered and how much should be consumed
12
• frequency of glucose and ketone monitoring and how to respond to presence of
ketones
• troubleshooting insulin delivery devices and dosage recommendations in event of
insulin pump failure
• glucagon minidose instructions
• vomiting and when to seek medical advice for same
• information on when and how to access health care team members.
5.3. Communication with health care team
Health care team availability by telephone facilitates communication, allows for earlier advice
and institution of sick day guidelines, and decreases or minimize clinical decompensation and
34-36
avoiding emergency room use as well as hospitalization.
5.4. Immunizations and influenza
During the influenza season, health care professionals should assess families' sick day man
aging knowledge and review sick day management plans. 37 Families should be advised of
the local recommendations regarding influenza and COVID vaccination. Where influenza and
pneumococcal immunizations are available and recommended, for example, in the United
States of America, during the influenza season, health care professionals should emphasize the
importance of these immunizations for persons living with diabetes. 37 Countries where multi
ple immunizations are available and recommended for pediatric age groups, health care porfes
sionals should encourage families to immunize their children and address any expressed bar
rieres to the uptake of immunizations, including concerns they may have regarding managing
minor side effects.
6. DIABETES MANAGEMENT FOR MILD ILLNESS AND KETOSIS
PREVENTION (FIGURE 2)
13
6.1. Insulin storage
The 'cold chain' should be reviewed. If the cold chain is not maintained to the point of purchase
(eg the pharmacy may store in a refrigerator, but it may have been exposed to high tempera
tures earlier, at the warehouse level, for example), or if transport and storage are not optimal
(eg carrying insulin home after purchase, or packing insulin in hold baggage during a flight –
insulin will freeze and then thaw), then insulin potency may be affected, leading to impaired
38 insulin action.
6.2. Insulin dose adjustments
Illnesses, especially when there is fever, raise glucose levels and require increasing insulin
doses. Commonly, an increase of basal and prandial insulin will be required to counteract the
effect of insulin resistance observed in acute illnesses, preventing ketosis. The following gen
Eral guidelines may be useful for these cases:
• If there is hyperglycemia without hyperketonemia or no more than small ketonuria, usual
recommendations are to give an additional, supplemental injection or bolus of rapid-acting
or short-acting insulin. Begin by giving the usual dose for carbohydrate coverage and cor
correction. Repeat correction dose if needed after 2-hours.
• Basal insulin doses, whether given as a long-acting insulin analog or intermediate insulin
in injection-based therapy, or as a basal rate when using an insulin pump may need to be
increased by 20-30%, depending on hyperglycemia magnitude.
• Higher prandial insulin doses, whether ultrarapid, rapid-acting or short-acting insulin, may
be required. For mild elevation of post-meal glucose levels, increase the calculated bolus
by 10%; wheareas in those cases where a moderate to large post-prandial elevation is pre
sent, an increase in 20% of the insulin boluses might be needed.
6.3. Insulin delivery and injection technique
14
When hyperglycemia occurs, besides adjusting insulin doses, care should be given to inadvert
ently stopped insulin delivery issues. It is essential that during illness, health care professionals
prompt parents and caregivers to assess for adequate insulin delivery. For insulin pen users
assess for:
• correct placement of pen needle, raised skin folds and skin infection
• a broken insulin cartridge holder
• excess air in the insulin cartridge
• the dose units counter not moving or moving incorrectly, and insulin not being delivered
ered when the dose button is depressed.
Checking for adequate insulin delivery is particularly important for insulin pump users, as ke
tones will develop within hours if there is a blocked or kinked pump infusion set. (See section
9 'Specific advice regarding sick day management for children and adolescents using diabetes
aid (insulin pumps, hybrid closed loop systems, glucose sensors)'.
6.4. Monitor glucose and ketones during mild illenesses for DKA prevention
As explained in the “Principles of sick days management”, glucose should be monitored every
1–2 hours and ketones every 2-4 hours. Urine glucose and urine ketone can be measured if
blood glucose and/or blood ketone monitoring equipment are/is not available. 24.25 Insulin ad
justments take place in order to allow insulin dosing according to glucose and ketone levels.
When CGM is used, the parents and teenager should keep in mind that capillary glucose
measurements are desirable when sick days occur, and the person is not feeling well.
Ketones should be measured every 2-4 hours. Blood ketone tests (for BOHB), or urine ketone
tests when blood ketone monitoring is unavailable, help to guide sick day management.:
• Blood BOHB ÿ0.6 mmol/l is abnormal in children with diabetes. 39.40
15
• Blood BOHB measurements may be especially valuable to prevent DKA in persons
who uses an insulin pump, as only short-rapid- or ultrarapid-acting insulin is used in this
type of therapy. Elevations in blood BOHB may precede elevations in urine ketones
41
due to interrupted insulin delivery (egTraces levels of ketones may be observed
related to fasting. These low levels should be treated with a meal and insulin dosing).
• During resolution of ketosis, blood BOHB normalizes sooner than urine ketones. 24.25
6.5. Monitor and maintain hydration with salt and water
Prevention of dehydration should be a priority during sick days. When vomiting, advise to take
small sips of cool liquids, which are better tolerated than warm liquids. Hydration can be helped
with frozen pops or frozen juice bars (either sugar-free in the setting of hyperglycemia, or
sugar-containing when glucose is <14mmol/mol, ~250 mg/dL)).
If appetite is decreased, replacing meals with easily digestible food (eg rice-lentil broths, rice
porridge and sugar-containing fluids) that provide energy (carbohydrates) can help prevent
starvation ketosis, as long as insulin is given. It may be helpful to remove excessive carbona
tion (bubbles) in some soft drinks to minimize potential for indigestion. Carbonated fluids may
alter the distribution of food within the stomach and may contribute to bloating in some per
42
sounds. Families should be advised to keep supplies to be used to prevent dehydration during
illness.
• glucose tablets, sweets or candies such as jelly beans or sucking candies as well as dried
fruits to prevent hypoglycemia
• clean (boiled/purified as necessary) water to provide hydration
• sugar and electrolyte containing fluids such as sports drinks, home-made lemonade
with sugar and salt, electrolyte mixtures, or sugar-containing soft drinks or sodas to
provide hydration, glucose, and salts
16
• easy to digest carbohydrates such as crackers, noodles, rice, rice porridge or yogurt
During gastrointestinal illnesses, it is reasonable to advise replacing meals with small volumes
of sugar-containing drinks for calories, provided with appropriate insulin coverage, along with
fluids that contain electrolytes, as noted above. A simple diet can be reintroduced that may
include rice, crackers, applesauce, bananas, tea, bread, yogurt, and potatoes, for example, de
pending on availability and local custom.
• Include sugar-containing drinks with insulin coverage.
• Give sufficient fluids to maintain hydration, keeping records of how much the child has
had to drink.
• Attend to urine output and follow body weight, if available at home, every 4–6 hours.
Steady weight suggests adequate hydration and fluid replacement, whereas ongoing
weight loss usually requires contact with the health care team to assess need for emer
gency room assessment or hospitalization for intravenous fluid treatment.
7. SICK-DAY MANAGEMENT WHEN VOMITING AND/OR GASTROINTESTI
NAL TRACT INFECTION.
7.1 Vomiting
Consider nausea and/or vomiting as a sign of insulin deficiency until proven otherwise.
Nausea and vomiting warrant care as vomiting can be caused by either:
• insulin deficiency resulting in hyperglycemia and ketosis and risk for DKA.
• an illness itself (ie gastroenteritis, unclean food or food poisoning, surgical
condition, other illness, etc.)
• severe hypoglycaemia
17
When vomiting occurs in a person with hyperglycemia and when ketosis is present, extra in
sulin must be administered, even when there is ongoing nausea and vomiting. In fact, the vom
iting may stop once extra insulin has been given, due to management of the ketosis.
If vomiting persists beyond 2 hours, especially in children under 5 years old, or if hypoglyce
mia cannot be corrected, refer for intravenous fluids with dextrose along with continued mon
itoring as reviewed in the Hypoglycemia Guideline (see ISPAD 2022 Clinical Practice Guide
lines Chapter 11 on Management of Hypoglycemia in Children and Adolescents with Diabe
your).
For vomiting in association with gastroenteritis, consider treatment with anti-nausea medica
tions, if available, and if there is no known allergy or other medical contraindication to such
treatment. Anti-nausea medications can include injectables or rectal suppositories of anti-emet
ics (eg ondansetron, promethazine, etc.), as oral intake of such medications may be difficult
with ongoing emesis. Some children/families have had success with oral anti-emetics like on
dansetron if given early in the course of the illness, or just after a bout of vomiting. Such med
ications would be contraindicated with any mental status changes. These medications also
should be used cautiously with food poisoning when they may be contraindicated. Addition
ally, if the nausea and vomiting are due to DKA treat as per ISPAD DKA Guideline (see ISPAD
2022 Clinical Practice Guidelines Chapter 13 on Diabetic Ketoacidosis and Hyperglycemic
Hyperosmolar State) as anti-emetics are contraindicated.
7.2 Gastrointestinal (GI) tract infections associated with hypoglycemia (Table 1).
GI tract infections, especially viral gastroenteritis, are associated with hypoglycemia. Occa
sionally, people with diabetes and families may report unexplained hypoglycemia as a prelude
to viral gastroenteritis, even prior to the first bout of emesis. Additionally, hypoglycemia may
continue beyond the symptomatic stage of nausea and vomiting, as malabsorption may persist
18
a few days longer as the gut heals. Frequent glucose monitoring can guide temporary insulin
dose reductions, recalling that insulin should never be totally stopped. 24-26,43,44
Reduce total daily insulin dose by 20–50% during GI illnesses associated with hypoglycemia
(Table 1), generally beginning with a 20% reduction of the basal or intermediate acting insulins
and a 50% reduction of the bolus dose, which may be given after eating to ensure intake of the
prepared drink and/or food. Ongoing frequent monitoring is needed because an excessive dose
reduction may lead to insulin deficiency and risk for ketosis and ketoacidosis.
Check ketones along with glucose levels as a guide to determine if starvation ketosis is occur
ring. Such ketones in association with hypoglycemia reflect inadequate energy supply and in
dictates a need for increased carbohydrate intake with insulin.
7.3. Consider Mini-Dose Glucagon for persistent hypoglycemia (Table 2)
If hypoglycemia persists with blood glucose levels <3.9 mmol/L (<70 mg/dL) along with nau
sea, vomiting, anorexia, or food refusal, a modified, smaller-than-usual dose of glucagon, if
available, can be given, termed 'mini-dose glucagon'. Glucagon Mini-Dose can increase the
glucose level back into a safe range as long as there are adequate glycogen stores in the liver,
which can be deficient following prolonged vomiting or fasting. Nevertheless, it is safe to try
33 45
mini-dose glucagon in such circumstances. The mini-dose is most easily administered
using an insulin syringe after reconstituting the glucagon with the diluent provided in the glu
crate kit. The dose begins with 0.02 mg (equal to 2 units on an insulin U-100 syringe) for
children up to age 2 years, and then increases by 0.01 mg (1 unit on an insulin syringe) per
year of life up to a max dose of 0.15 mg (15 units on an insulin syringe). The mini-dose can be
repeated after 30-60 minutes, if needed. If hypoglycemia persists and/or glucagon is not avail
able, emergency services will be required for intravenous fluids containing dextrose. Of note,
19
intranasal preparations of glucagon for easier administration have been studied and are availa
46
wheat in many countries (Baqsimi, 3 mg for all children from 4 years). A stable ready-to-use
47 .
solution of dasiglucagon for emergency subcutaneous administration is also underway
Oral medicines for symptomatic relief of gastroenteritis have no proven efficacy and are there
fore not usually recommended. Infectious diarrheal illnesses are best managed in their locales
when the local health care teams should be aware of the proper medications, and if any are
indicated. Unknown or uncertain alternative medicines should be avoided; sick day education
efforts should include discussion of safe and unsafe management efforts with a review of all
medications.
8. TREATMENT OF KETOSIS (FIGURE 3)
8.1. Ketone monitoring
BOHB levels guide treatment since increasing blood levels of ketones correlate with decreas
ing pH levels and reflect the severity of the clinical status. On the other hand, blood ketone
levels decline directly in response to insulin therapy. 24,25,35,41 . Caution should be taken when
treatment decisions are based on ketonuria, as persistent ketonuria may be due to the slow
clearance of AcAc. In response to insulin therapy, BOHB levels commonly decrease long be
fore AcAc levels do. The frequently employed nitroprusside test only detects AcAc in blood
and urine, and so routine urine ketone monitoring often shows prolonged ketonuria even when
48
significant ketoacidosis and hyperketonemia have already responded to treatment.
• BOHB levels lower than 0.9 nmol/L or traces of urinary ketones may correspond to
ketosis starvation.
• BOHB levels 1-2.9 mmol/L may be treated at home. In fact, declines in BOHB levels
will be clinically evident even before declines in glucose levels. with frequent fast
20
acting insulin analogs. BOHB may rise within the first hour but will almost always
have decreased 2 hours after a successful administration of extra insulin.
• BOHB levels greater or equeal than 3 mmol/L or large urine ketosis suggest ketoaci
dosage and treatment for DKA should be considered. emergency department transfer
should be performed. In some cases, starvation ketones may rise > 3 mmol/l, and then
a pH is necessary to discern between DKA and starvation ketones.
8.2. Hydration
When ketosis is present, hydration becomes a cornerstone of treatment to avoid water and
electrolyte imbalance that may progress to acidosis and DKA. 4.24-26.43.44.48Frequent

. small sips
of liquids containing water and electrolytes should be given every 5-10 minutes. Volume of
fluids may be calculated wither 4-6 ml/kg/hr or 100 ml/hr, approximately. For those cases that
have glucose levels of < 14 mmol/l (~250 mg/dL), glucose containing liquids should be ad
ministered. When hyperglycemia above 14 mmol/l (~250 mg/dL) and ketosis is observed, oral
hydration should where possible contain salt, but no glucose.
8.3. Insulin Adjustment
When ketosis is present, frequent additional doses of ultrarapid, rapid-acting or short-acting
insulin are required to turn off ketogenesis, reduce glucose levels, and prevent progression to
ketoacidosis and hospital admission. 24,25,48,49Several

. methods for calucating supplemental in
sulin doses are practiced around the world. All of these methods consider that the dose and
frequency of subcutaneous bolused insulin will depend on the severity of ketosis and the level
and duration of hyperglycemia. The safest approach in the individual case would be to follow
local instructions if these are well grounded.
Supplemental doses of subcutaneous rapid-acting insulin analog (insulin lispro, aspart, glulis
ine) should be repeated every 1-2 hours if ketosis is severe, and every 2-4 hours if ketosis is
21
mild. Short acting (regular) insulin repeated every 2-4 hours may be used if insulin analogs are
not available. Frequent glucose and ketone monitoring results will guide the frequency and
extra insulin that should be used in successive insulin dosing. The most frequently used meth
ods for treating hyperglycemia and ketosis are based on on body weight, increased correction
doses by 10-20%, and doses as a percentage of TDD (total daily insulin dose).
A. Body Weight Method.
1-2 hourly SC rapid-acting insulin analog (insulin lispro or insulin aspart) is safe for
treatment of ketosis. 50-54
• The dose of 0.1 to 0.15 units/kg is a general recommendation for children
and adolescents with standard insulin requirements of approximately 0.7-1.0
units/kg/day. However, for children or adolescents who have low usual daily
insulin requirements, or those with insulin resistance and high daily insulin re
quirements, the percentage calculations may work more readily rather than the
empirical units/kg additional dose.
• When children or adolescents are in the “honeymoon” remission phase and in
sulin doses are relatively small, there may be a need to increase supplemental
insulin doses; consider providing additional doses per kg as noted above
(~0.05-0.1 units/kg) and assess response, as the standard supplemental dose of
10-20% of the TDD may be insufficient to lower the glucose levels in a timely manner
manner.
B. Percentage Increase Method
Where diabetes is managed on a glucose and meal adjusted regime, the additional in
sulin dose for ketosis can be calculated as a percentage increase of the dose calculated
based on the insulin sensitivity/correction factor. The caregiver calculates the usual
22
dose to correct hyperglycemia and increases the dose by 10% when mild ketosis is
present and by 20% when ketosis is moderate/severe. If ketosis does not improve, one
can also give 150-200% of the calculated correction dose, repeated every 2-4 hours,
based on response. For example, a child has a glucose level that would typically require
5 units to correct, but in the presence of moderate ketones the caregiver would increase
the dose by 20% and give 6 units.
C. Total Daily Dose (TDD) Method
With this method the caregiver should calculate the total daily dose (TDD) defined as
the total of rapid/short acting and long/intermediate acting insulins for the day (or the
total of bolus and basal insulin given by a pump). This method is based on giving 10-
20% a of TTD for treatment of ketosis.
9. INSULIN PUMPS AND HYBRID CLOSED LOOP SYSTEMS
The key points of sick day management, mentioned previously, are the same for insulin pump
to and hybrid closed loop users, as for those receiving insulin injections. 44,55,56 Some points
highlight for pump users are the following:
9.1. Hyperglycemia and risk for DKA
People on an insulin pump use only rapid- or short-acting insulin and do not have any in
jected depot of long-acting insulin, so DKA can develop rapidly with either interruption of
insulin delivery, or during an intercurrent illness when no increased insulin is given. Blood
BOHB measurements may be especially valuable to prevent DKA in people who use an blind
linen pump. Elevations in blood BOHB may precede elevations in urine ketones due to inter
41
broken insulin delivery. Episodes of hyperglycemia must be taken very seriously, espe
cially if associated with elevated blood or urine ketones.
23
If the glucose level is 14 mmol/L (~250 mg/dL) or above check for problems with insulin
pump or delivery system. Common problems include kinks in the catheter, air in the infusion
line, cat bites on tubing causing a hole, leakage at connections, disconnected catheters espe
cially at the insertion site, and insertion site irritation. Refresh the insulin cartridge and replace
the insulin needle, tubing and catheter. Extra boluses should be given to correct hyperglycemia
and ketonemia (Figure 2 and 3). After extra insulin has been given, the blood ketone level may
temporarily increase by 10–20% for the first hour or two but should be expected to decrease
thereafter. If it has not decreased, repeat dose with insulin from a new cartridge/vial. Do not
use an insulin pump for extra insulin in this situation.
Use temporary basal rate increases from 20% to 50%, or higher until the glucose level improves
and ketone levels return to normal (BOHB <0.6 mmol/L or negative to small urine ketones).
Note, it may be necessary to increase the maximum hourly basal rate that the pump can deliver
when using temporary basal rate increases for sick day management.
If blood ketone level is ÿ3 mmol/L (or the urine ketones remain large) despite extra insulin
and hydration, consider referral to the emergency room for assessment and intravenous flu
ids, as the risk for DKA is high.
9.2 GI illnesses and hypoglycemia
Meal insulin boluses may need to be decreased during GI illnesses, as noted above, when hy
poglycemia is a concern. Basal insulin rates can also be decreased by 20-50% when hypogly
cemia is a concern, as a temporary basal rate reduction for 2-4 hours or longer, as needed based
on ongoing glucose and ketone monitoring. If ketones appear, the insulin dose has been de
creased too much.
9.3. Closed-loop technologies
Current closed-loop technologies, combining both insulin pumps and sensors, and their inter
active regulation by artificial intelligence systems (hybrid closed loop systems, AID), are up-
24
coming systems in all pediatric age groups, including toddlers 57 58. They have the potential and-
to substantially increase time in range and therefore metabolic control 59.60 . Several systems
incorporate customizable glucose targets and user-initiated modes to reduce or intensify in
sulin delivery in special situations 61. These tools make closed loop systems helpful to keep the
glucose levels in target during sick days. However, if in doubt, it may be better to run a hybrid
closed loop in manual mode during sickness. Subsequent correction boluses are increased by
10-20% during the period of illness, according to the glucose and ketone results, and can be
given by pump once the infusion has been changed. If glucose levels are high and vomiting or
illness occurs accompanying ketone measurements are important. If ketones are 0.6 or higher
or vomiting occurs, closed loop should be stopped and sick day management should run in
open loop or manual mode following regular sick day rules, to ensure adequate supplemental
62
insulin delivery.
9.4. Hospitalization
Hospitalized persons using insulin pump treatment need advice whether or not pump use can
be continued during hospitalization. The conclusion depends on the ability of the person to
safely operate the pump, availability of insulin pump supplies and the health care team´s fa
miliarity with pump treatment. Experienced pump users may be encouraged to continue their
pump treatment during hospitalization as some studies have shown fewer episodes of severe
hyperglycemia and hypoglycemia and that most persons could use their pump safely in the
inpatient setting. Reasons for discontinuing pump treatment during hospitalization might be
lack of pump supplies, malfunction of the pump, altered level consciousness, and threats of
63 suicide. Similar to insulin pump use, closed loop use in hospitalized persons can be suc
cessful, if health care teams are up to date and familiar with these new diabetes technologies
64 .
25
10. ADJUNCTIVE THERAPY
Adjunctive use of the new class of oral agents called SGLT2 (or SGLT1/2) inhibitors have
been reported to increase risk for DKA in persons with T1D or type 2 diabetes. The greatest
concern stems from the DKA risk, which can occur at times in the absence of extreme hyper
glycemia (euglycemic DKA), especially in the setting of 'low carb' diets or low carbohydrate
65.66
intake or associated with dehydration. Any person receiving SGLT1/2 inhibitors must re
ceive rigorous sick day management education and strategies for mitigating DKA risk need to
be discussed to avoid progression to DKA. This includes training on the use of blood ketone
monitoring of BOHB as atypical or euglycemic DKA has been reported and therefore typical
blood glucose warning levels for DKA may be inadequate if SGLT1/2 inhibitors are being
taken. SGLT-2 inhibitors should be stopped whenever the person is feeling unwell or ketones
arise. 67.68
11. LOW CARBOHYDRATE DIETS
Low carbohydrate diets have gained increased popularity in the past recent years, also in chil
dren with diabetes, but outcomes have been controversial. Clinical trials are ongoing – aiming
to get validated information about diabetes-specific quality of life with low carb diet and out
69
70 come in metabolic control . Of concern is the high risk for hyperketonemia, especially in
sick children; low carbohydrate or very low carbohydrate diets might lead to DKA. People
need to be aware that beside a potential anthropometric deficit and higher cardiovascular risk
metabolic profile especially during episodes of acute illness occurrence of DKA is a notable
71 risks . The higher risk for DKA could be mitigated by increased monitoring of ketone body
72
production due to measurements of ketones in blood . Possibly newer technologies like ke
73-75
tone sensors might improve ketone monitoring in future .
26
Conflicts of interest:
LML has consulting activities unrelated to the current manuscript with the following: Astra
Zeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Eli Lilly and Company,
Insulet, Johnson & Johnson, MannKind Corporation, Merck, Novo Nordisk Inc., Roche Diag
nostics. Sanofi US, and Unomedical.
CL has consulting activities unrelated to the current manuscript with Sanofi and Eli Lilly.
JW has research grants unrelated to the current manuscript from the following: AstraZeneca,
Novo Nordisk, Boehringer Ingelheim, and MannKind.
SHE has received lecturing honoraria from Eli Lilly, Sanofi, Medtronic, Pfizer, Insulet and
Vertex.
RH has consulting activities unrelated to the current manuscript with Abbott, AstraZeneca and
NovoNordisk. There are no reported conflicts from HP and AV.
WL has consulted for NovoNordisk previously, and received speaking honoraria from Eli
Lilly, Sanofi, Medtronic, Merck. None of these activities have conflicts with the current man
uscript.
27
28
29
30
31
32
TABLE 1. NORMOGLYCEMIA/HYPOGLYCEMIA
KETONES (starvation) BLOOD GLUCOSE
< 5.0 mmol/L < 5.0 - 10 mmol/L
BLOOD URINE
90 mg/dL 90 - 180 mg/dL
• No extra insulin •
Reduce TDD insulin 20% •
< 0.6 mmol/L Negative/trace Oral sugar fluids and extra CHO (*) • If • No extra insulin
BG < 70mg/dl (3.9 mmol/l)ÿ Hypo correction (consider mini-dose
of glucagon )
• Reduce TDD insulin 15% •
0.6 – 0.9 Give ordinary bolus • Oral • Oral sugar fluids •
Trace/small
mmol/L sugar fluids • Extra CHO (*) Extra CHO (*)
• Oral sugar fluids • • Give ordinary bolus •

1 – 1.4 mmol/L small/moderate Extra CHO (*) Oral sugar fluids • Extra
• Give correction bolus according to ISF when blood glucose has risen over 5-6 mmol/l (90-110 mg/dl) CHO (*)
• Add +5% TDD or 0.05 U/Kg to

1.5 – 2.9 • Do not reduce TDD insulin ordinary bolus • Oral sugar fluids
Moderate/wide
mmol/L • Oral sugar fluids • • Extra CHO (*)
Extra CHO (*)
• Give correction bolus according to iSF when blood glucose has risen over 5-6 mmol/l (90-110 mg/dl)
• Add +5% TDD or 0.05 U/Kg to
• If vomiting, cannot eat or drink, consider IV Saline +5% glucose solution
ÿ 3 mmol/L wide ordinary bolus
Risk of Ketoacidosis
CHECK FOR BG AND KETONES EVERY 2 HOURS
(*) extra carbohydrates if tolerated; BG, blood glucose; TDD, total daily dose, CHO, carbohydrate. Ordinary bolus = usual correction and/or carbs insulin. •
To calculate the TDD, add up all the insulin given on a usual day (ie short/ rapid and long/ intermediate acting) or sum daily basal rates and boluses in a pump.
• include additional boluses given for correction of hyperglycemia.
• Recalculate the ISF (Insulin Correction Factor) each day during illness to account for the increase in insulin resistance that the illness causes
33
• In children and adolescents with usual low (<0.7U/kg/day) or usual high ( >1 U/kg/day) insulin requirements, consider using the percentage (%) calculation rather than empirical 0.05- 0.1 -0.2 U/kg additional
dose.
• High BG and elevated ketones indicate a lack of insulin.
• “Starvation” blood ketones” are usually <3.0 mmol/L.
• When the child is feeling sick or vomiting and ketone levels are negative or low (trace or small) with BG < 10-14mmol/L (< 180-250 mg/dl), he/she must try to drink sugar-containing
fluids in small amounts (at least 100ml/h) to keep BG up.
• When ketone levels are elevated, priority is to give extra insulin. If BG is simultaneously low, IV saline 5% dextrose solution may be required.
• Additional doses of insulin are always short or rapid-acting. Short-acting insulin can be given intramuscularly to speed up absorption.
• The ketone level may increase slightly (10-20%) within the first hour after giving extra insulin, but afterwards it should decrease. • Blood ketones
(BHOB) normalize sooner than urine ketones.
• If the child's glucose levels are persistently elevated or the illness is expected to last ÿ3days, consider increasing long/ intermediate acting insulin or the basal rates delivered by pump by 10-20% (even higher,
up to 50% by pump at times, if needed) during the expected sick days and reduce gradually as the illness subsides. [E]
Table 2: Recommended dose for mini-dose glucagon
Age (years) Quantity
micrograms mg cc’s (1mg/cc) units on insulin sy
ring
<2 20 0.02 0.02 2
2-15 10 per year of age 0.01 per year of age 0.01 per year of age 1 per year of age
>15 150 0.15 0.15 15
Note that the doses recommended above are quite different (lower) from emergency doses given in case of severe hypoglycemia
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ISPAD 2022 Sick Day Management Guidelines

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ISPAD 2022 Sick Day Management Guidelines

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Machine Translated by Google

ISPAD CLINICAL PRACTICE CONSENSUS GUIDELINES 2022

and adolescents with diabetes

Helen Phelana ,Jamie

at John Hunter Children's Hospital, Newcastle, New South Wales, Australia

Department of Pediatrics, Medical University of Innsbruck, Austria

Running title: Sick Day Management in Diabetes

Word count: 6649

1. WHAT'S NEW IN SICK DAY MANAGEMENT?

2. EXECUTIVE SUMMARY AND RECOMMENDATIONS

3. THE EFFECT OF ILLNESS ON DIABETES

4. SICK DAY DIABETES MANAGEMENT PRINCIPLE

5. PREPARATION FOR SICK DAYS

6. DIABETES MANAGEMENT FOR MILD ILLNESS AND KETOSIS

7. SICK-DAY MANAGEMENT WHEN VOMITING AND/OR GASTROINTESTI

NAL TRACT INFECTION

1. WHAT'S NEW IN SICK DAY MANAGEMENT?

diabetes for prevention of ketones and management with new technologies.

precipitate persist increases in insulin requirements for days or weeks.

• Anticipatory guidance to deal with conditions of predictable patterns of increased in

sulin requirements, such as chronic conditions requiring steroid therapy or hyperglyce

with sick day management.

regulation by artificial intelligence systems (hybrid closed loop systems, automated in

user-initiated modes to reduce or intensify insulin delivery in special situations.

2. EXECUTIVE SUMMARY AND RECOMMENDATIONS

2.1. Sick day preparation

People with diabetes, their families and/or caregivers

diabetes during illness. This education should be delivered at diagnosis, at follow-up at

at least annually, and opportunistically [C].

• should be taught to proactively adjust diabetes therapy to prevent uncontrolled or symp

tomatic hyperglycemia, dehydration, hyperglycemic ketosis, ketoacidosis, hypo

normoglycemic ketosis and/or severe hypoglycemia [E].

2.2. Management for ketosis prevention

bridge, line and catheter to ensure adequate insulin delivery [B].

• Monitor glucose and ketone levels at least 1-2 hourly.[E]

reduce emergency room visits and hospitalizations [B].

below 0.6 mmol/l [E].

o Oral fluids containing carbohydrate should be consumed if the glucose level

is below 14 mmol/l (250 mg/dl); carbohydrate-free fluids should be given

when glucose is above 14 mmol/l (250 mg/dl).

o Consider timely initiation of intravenous fluids if the child is unable to drink

services and the family [E].

o the child's condition deteriorates

o the underlying condition is unclear

oh caregiver understanding/language problems make it difficult to com

communicate with the family

oh there are co-morbid conditions (eg Down Syndrome, disordered eating

behaviors, mental illness, epilepsy, inflammatory bowel disease, ma

laria, parasitic infections, etc.)

o the child is very young (less than 5 years old)

2.3. Management when vomiting and/or gastrointestinal illness present

• Hypoglycemia with hyperketonemia, which may occur in the setting of gastrointestinal

nal llness or starvation, requires administration of insulin along with carbohydrate

• Gastrointestinal illnesses, especially gastrointestinal viruses, are the most frequent

o weight loss continues, suggesting worsening dehydration and potential cir

o vomiting persists beyond two hours (particularly in young children)

o unable to keep glucose level > 3.9mmol/mol (70mg/dl)

o if hypoglycemia cannot be corrected, refer for intravenous fluids with dex

trose along with continued monitoring.

2.4. Management where ketosis suspected or confirmed

carbohydrate-containing drink if glucose level is below 14 mmol/l (250 mg/dl). Aim

• Give frequent additional doses of ultrarapid, rapid-acting or short-acting insulin to treat